Unilateral Sinus Disease: What Is, and Is Not Odontogenic Sinusitis?

The differential diagnosis of unilateral sinus disease (USD) is broad, and while concerning etiologies like sinonasal neoplasia, invasive fungal sinusitis, and cerebrospinal fluid rhinorrhea should always be considered, most cases are due to noninvasive inflammatory or infectious conditions. To diagnose USD appropriately, clinicians must integrate the clinical history and examination, nasal endoscopy, computed tomography (CT), and possibly MRI. Odontogenic sinusitis (ODS) is the most common cause of unilateral maxillary sinus opacification on CT, with 45% to 75% of such cases being odontogenic in nature. This study provides USD diagnostic considerations and reinforces the diagnostic approach to ODS.

Collaboration between otolaryngologists and oral surgeons in maxillary sinus elevation planning.

BACKGROUND: The collaboration between otolaryngologists and dental providers is crucial for the planning and execution of maxillary sinus elevation (MSE) procedures, which are integral to successful dental implant placements. PURPOSE: This article examines the essential role of otolaryngological assessments in identifying potential sinonasal risks that could impact the outcomes of MSE. MATERIALS AND METHODS: A comprehensive narrative review of existing literature was conducted. DISCUSSION: The review underscores the importance of thorough preoperative evaluations, including patient history, computed tomography (CT) or cone-beam CT (CBCT) scans, and nasal endoscopy, to mitigate sinonasal health risks. It details various clinical scenarios and patient assessments, emphasizing a systematic approach to diagnosing and managing sinonasal conditions proactively. The discussion reveals that while some sinus conditions may not significantly affect MSE success, conditions impacting mucociliary clearance and sinus drainage are critical risk factors requiring otolaryngological intervention. Additionally, the article introduces a grading system to assist clinicians in identifying patients who would benefit from otolaryngological evaluations prior to MSE. CONCLUSION: This review highlights the value of interdisciplinary collaboration and standardized protocols in enhancing the predictability and safety of MSE procedures, ultimately improving patient outcomes.

Maxillary Antrostomy Versus Complete Sinus Surgery for Odontogenic Sinusitis With Frontal Sinus Extension.

OBJECTIVES: Endoscopic sinus surgery (ESS) is often necessary when managing odontogenic sinusitis (ODS), but ESS extent for ODS with extramaxillary sinus involvement has been incompletely studied. This study compared outcomes after wide maxillary antrostomy (MA) alone versus complete ESS for ODS with frontal sinus involvement. METHODS: A multicenter prospective cohort study was conducted on patients with uncomplicated ODS (no extrasinus spread) who underwent ESS when computed tomography demonstrated maxillary, anterior ethmoid (AE), and frontal sinus opacification. Multiple preoperative and postoperative variables were recorded, including 22-item sinonasal outcome tests (SNOT-22) and endoscopic findings. Ultimate SNOT-22 and endoscopic resolution, and time to SNOT-22 and endoscopic resolution were compared between patients who underwent MA alone versus "complete" ESS (maxillary, ethmoid, frontal; not sphenoid). RESULTS: Of 70 patients, mean age was 59.2 years, and 55.7% were male. Thirty-five underwent MA alone, and 35 had complete ESS. At first postoperative visits (mean 9.3 days), AE sinus purulence was more likely resolved after complete ESS compared with MA (97.1% vs. 71.4%, p = 0.006). However, time to resolution of AE purulence was comparable by 6 weeks postoperatively (p = 0.158). There were no significant differences in times to foul smell resolution and achieving ≥9 point SNOT-22 reduction (p > 0.05). CONCLUSIONS: For ODS with frontal sinus involvement, MA alone and complete ESS both resulted in rapid and long-term symptomatic resolution. While ultimate resolution of sinus purulence was equivalent between surgery groups, complete ESS did lead to faster resolution of frontoethmoidal purulence in a significant number of cases. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

Subtotal Middle Turbinate Resection in Patients with Chronic Rhinosinusitis with Nasal Polyps is Unlikely to Cause Empty Nose Syndrome: A Multi-Institutional Prospective Study.

BACKGROUND: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. METHODS: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up. RESULTS: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. CONCLUSIONS: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Sinus Evaluation for Odontogenic Sinusitis.

This article summarizes how to diagnose common and nuanced cases of odontogenic sinusitis (ODS) through a collaborative approach between otolaryngologists and dental specialists, with a heightened focus on the role of otolaryngologists in the diagnostic process. A critical part of the diagnostic framework is that otolaryngologists must confirm the infectious sinusitis but also suspect ODS to ensure he or she refers the patient to a dental specialist to confirm or refute ipsilateral infectious maxillary dental pathology. To confirm the purulent sinusitis of ODS, nasal endoscopy is most critical. Computed tomography imaging is an important part of the workup.

Maxillary sinus opacification after surgery in asymptomatic patients: Transient swelling of the sinus mucosa or graft dispersion into the maxillary sinus. A radiographic report of three cases after a follow-up period of at least 5 years.

Maxillary sinus grafting is a predictable regenerative technique to facilitate maxillary posterior implant placement when there is insufficient vertical bone height inferior to the maxillary sinuses to allow placement of implants of adequate dimensions. It enables an increase in vertical bone height, which makes implant placement easier. Maxillary sinus mucosal membrane perforation is one of the most common intraoperative complications during maxillary sinus grafting and may result in extrusion of graft material into the sinus. When this occurs, the mucociliary function of the maxillary sinus may expel the extruded graft material through its natural ostium, though graft particles may remain in the sinus or possibly occlude the natural ostium. After grafting, transient maxillary sinus mucosal oedema may occur. A postoperative CBCT scan may reveal varying degrees of sinus opacification, namely partial, subtotal or total. Although it is always possible to identify graft material, which may enter the sinus as a result of membrane perforation that might not even be visible to the implantologist during the surgical procedure, it is challenging to assess whether sinus opacification is due to mucosal thickening or mucus accumulation. The aim of the present case series was to offer a pragmatic approach to managing asymptomatic patients whose CBCT scans demonstrated partial, subtotal or total maxillary sinus opacification with bone graft particles that seemed to have been extruded into the sinus.

Reliability of large language models in managing odontogenic sinusitis clinical scenarios: a preliminary multidisciplinary evaluation.

PURPOSE: This study aimed to evaluate the utility of large language model (LLM) artificial intelligence tools, Chat Generative Pre-Trained Transformer (ChatGPT) versions 3.5 and 4, in managing complex otolaryngological clinical scenarios, specifically for the multidisciplinary management of odontogenic sinusitis (ODS). METHODS: A prospective, structured multidisciplinary specialist evaluation was conducted using five ad hoc designed ODS-related clinical scenarios. LLM responses to these scenarios were critically reviewed by a multidisciplinary panel of eight specialist evaluators (2 ODS experts, 2 rhinologists, 2 general otolaryngologists, and 2 maxillofacial surgeons). Based on the level of disagreement from panel members, a Total Disagreement Score (TDS) was calculated for each LLM response, and TDS comparisons were made between ChatGPT3.5 and ChatGPT4, as well as between different evaluators. RESULTS: While disagreement to some degree was demonstrated in 73/80 evaluator reviews of LLMs' responses, TDSs were significantly lower for ChatGPT4 compared to ChatGPT3.5. Highest TDSs were found in the case of complicated ODS with orbital abscess, presumably due to increased case complexity with dental, rhinologic, and orbital factors affecting diagnostic and therapeutic options. There were no statistically significant differences in TDSs between evaluators' specialties, though ODS experts and maxillofacial surgeons tended to assign higher TDSs. CONCLUSIONS: LLMs like ChatGPT, especially newer versions, showed potential for complimenting evidence-based clinical decision-making, but substantial disagreement was still demonstrated between LLMs and clinical specialists across most case examples, suggesting they are not yet optimal in aiding clinical management decisions. Future studies will be important to analyze LLMs' performance as they evolve over time.

Using Ipratropium Bromide Nasal Spray Response as a Screening Tool in the Diagnostic Workup of Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: Unilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta-2 transferrin electrophoresis has been the gold standard for initial non-invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis-related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea. METHODS: A prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta-2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body-mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables. RESULTS: Twenty patients had CSF rhinorrhea, and 53 had non-CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body-mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea. CONCLUSIONS: In patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:56-61, 2024.

Cadaveric and Computed Tomography Analysis of the Anterior Ethmoidal Artery Flap.

BACKGROUND: The anterior ethmoidal artery (AEA) flap has been successful in repairing anterior nasal septal perforations and has been presumed to be axially based on AEA branches coursing through or around the cribriform plate (CP). However, limited evidence supports the flap's axial supply. The purposes of this cadaveric and computed tomography (CT) study were to assess the arterial anatomy from the CP to the septum, and to determine AEA flap length to predict ideal flap base width. METHODS: Ten fresh latex-injected cadavers were utilized for endoscopic dissection to identify arteries traversing the CPs on each side. First, arterial trajectories along the dorsal septum were recorded. Measurements were then made bilaterally along the septum from the middle turbinate (MT) axilla to the nasal branch of the AEA (NBAEA) traversing the CP. Additionally, 100 sinus CTs were reviewed to measure AEA flap lengths bilaterally. RESULTS: From 10 cadavers, 20 sides were utilized for measurements. In all cadavers, the AEA septal branches coursed diagonally or horizontally along the dorsal septum, and never directly vertically. The mean distance from the MT axilla to the NBAEA was 1.24 ± 1.93 cm (range = 1-1.5 cm). Based on CTs, the mean AEA flap length was 6.40 ± 0.60 cm. CONCLUSIONS: Based on the non-vertical courses of AEA septal branches, the AEA flap is more likely a random transposition flap than an axial flap. Average AEA flap length ranged from 6.0 to 7.0 cm. Assuming 3:1 length:width ratios, AEA flap base widths should be about 2.0-2.3 cm. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2100-2104, 2024.

Nasoseptal Flap to Repair Large Maxillary Sinus Floor Defects.

This case highlights the successful use of a large nasoseptal flap to repair a large maxillary sinus floor defect. Surgeons can therefore rely on this flap for repairing maxillary sinus floor defects of most sizes and locations. Laryngoscope, 134:87-91, 2024.

Systematic review of errors on beta-2 transferrin gel electrophoresis testing of rhinorrhea and otorrhea.

BACKGROUND: Beta-2 transferrin (B2-Tf) gel electrophoresis (GE) is the preferred non-invasive diagnostic modality for confirming cerebrospinal fluid (CSF) in body fluids. While B2-Tf GE testing is highly sensitive and specific for CSF, false-positive (FP) and false-negative (FN) results can lead to diagnostic and therapeutic dilemmas. Several series have demonstrated potential causes of false B2-Tf GE results, but few studies have reported reasons for these errors. The purpose of this systematic review was to describe sources of B2-Tf GE errors. METHODS: A systematic review was performed by searching OVID, EMBASE, and Web of Science databases for B2-Tf GE studies. After applying exclusion criteria, original research studies directly addressing erroneous B2-Tf GE results underwent qualitative analysis. RESULTS: Of the 243 abstracts screened, 71 underwent full-text review and 18 studies reporting B2-Tf GE errors were included for analysis. There were 15 potential FPs, 12 actual FPs, 12 potential FNs, 19 actual FNs, and 14 indeterminate results. There were also 246 potentially indeterminate results from in vitro studies. Reasons for B2-Tf GE errors included serum transferrin alterations (n = 17; all potential), infection related (n = 13; 9 potential), orbital or salivary contamination (n = 2; 1 potential), and collection related (n = 255; 246 potential). There were 31 false or indeterminate results with unspecified reasons. There were no reported errors due to laboratory processing. CONCLUSIONS: Multiple potential or actual reasons for false or indeterminate results have been reported for B2-Tf GE testing of rhinorrhea and otorrhea. Future studies should explore reasons for B2-Tf testing errors and how these may affect clinical decision making.

Cadaveric analysis of autonomic nerve fiber density in posterior nasal, posterolateral nasal, and anterior ethmoid nerves.

KEY POINTS: Autonomic nerve densities were equivalent in posterior nasal (PNN), posterolateral nasal (PLNN), and anterior ethmoid nerves (AEN). Rhinitis studies should explore the utility of PLNN and/or AEN transection over PNN alone.

Total times to treatment completion and clinical outcomes in odontogenic sinusitis.

BACKGROUND: Multidisciplinary collaboration is essential for effective odontogenic sinusitis (ODS) management. One point of debate has been the optimal timing of primary dental treatment and endoscopic sinus surgery (ESS), but differences in time to completion of these treatment pathways have not been studied. METHODS: A retrospective cohort study was conducted on ODS patients from 2015 to 2022. Demographic and clinical variables were recorded, and various durations of time were analyzed from rhinologic consultation through treatment completion. Resolution of sinusitis symptoms and purulence on endoscopy was also recorded. RESULTS: Eighty-nine ODS patients were analyzed (47.2 % male, median 59 years-old). Of the 89 ODS patients, 56 had treatable dental pathology, and 33 had no treatable dental pathology. Median time to treatment completion for all patients was 103 days. Of 56 ODS patients with treatable dental pathology, 33 had primary dental treatment, and 27 (81 %) required secondary ESS. In patients who underwent primary dental treatment followed by ESS, median time from initial evaluation to treatment completion was 236.0 days. If ESS was pursued primarily followed by dental treatment, median time from initial evaluation to treatment completion was 112.0 days, which was significantly shorter than if dental treatment was pursued primarily (p = 0.002). Overall symptomatic and endoscopic resolution was 97.8 %. CONCLUSIONS: After dental and sinus surgical treatment, ODS patients experienced 97.8 % resolution of symptoms and purulence on endoscopy. In patients with ODS due to treatable dental pathology, primary ESS followed by dental treatment resulted in a shorter overall treatment duration than primary dental treatment followed by ESS.

Clinical Features and Headache Diagnoses in Patients With Chief Complaint of Craniofacial Pain.

OBJECTIVES: Investigate the use of nasal endoscopy, sinus imaging, and neurologic evaluation in patients presenting to a rhinologist primarily for craniofacial pain. METHODS: This was a retrospective analysis of consecutive outpatients presenting to a rhinologist between 2016 and 2019 with chief complaints of craniofacial pain with or without other sinonasal symptoms, who were then referred to and evaluated by headache specialists. Data analyzed included sinusitis symptoms, Sino-Nasal Outcome Test (SNOT-22) scores (and facial pain subscores), pain location, nasal endoscopy, computed tomography (CT) findings, and headache diagnoses made by headache specialists. RESULTS: Of the 134 patients with prominent craniofacial pain, the majority of patients were diagnosed with migraine (50%) or tension-type (22%) headache, followed by multiple other non-sinogenic headache disorders. Approximately 5% of patients had headaches attributed to sinusitis. Amongst all patients, 90% had negative nasal endoscopies. Patients with negative endoscopies were significantly less likely to report smell loss (P = .003) compared to those with positive endoscopies. Poor agreement was demonstrated between self-reported pain locations and sinus findings on CT (kappa values < 0.20). Negative nasal endoscopy showed high concurrence with negative CT findings (80%-97%). CONCLUSIONS: Patients presenting with chief complaints of craniofacial pain generally met criteria for various non-sinogenic headache disorders. Nasal endoscopy was negative in 90% of patients, and CT demonstrated poor agreement with pain locations. Nasal endoscopy and CT shared high concurrence rates for negative sinus findings. The value of nasal endoscopy over sinus imaging in craniofacial pain evaluation should be explored in future studies.

Inflammatory endotype of odontogenic sinusitis.

BACKGROUND: Odontogenic sinusitis (ODS) is distinct from non-odontogenic rhinosinusitis with regard to clinical features as well as diagnostic and therapeutic approaches. While numerous studies have explored immune profiles of chronic rhinosinusitis, very few studies have explored the inflammatory endotype of ODS. METHODS: Odontogenic sinusitis was diagnosed by confirming infectious sinusitis adjacent to infectious maxillary odontogenic pathology. Maxillary sinus cultures and mucosal biopsies were obtained during endoscopic endonasal surgery in ODS and control patients. Controls were patients undergoing endoscopic skull base surgery with no sinus disease. Specimens were snap frozen in liquid nitrogen and stored at -80°C. Analysis was performed using a multiplex assay to measure Th-1 (TNFα, IFNγ, IL-2,12,18), Th-2 (IL-4,5,9,13), Th-17 (IL-17A,17F,22), and innate (CCL5,CXCL9,CXCL10, IL-6,8,10,12,23,27) immune pathways. Groups were compared via independent sample t-tests; if assumptions were violated, nonparametric Wilcoxon ranked sum tests were performed. RESULTS: Specimens from 22 ODS patients were compared to nine controls. ODS mucosal tissue was sampled in the setting of the following dental pathologies: post-dental extraction (n = 15), untreated apical periodontitis (n = 2), apical periodontitis after root canal therapy (n = 2), and maxillary sinus bone grafting with or without dental implantation (n = 3). The following cytokines were significantly elevated in ODS compared to controls: IFNγ, TNFα, IL-6, 8, 10, 27, and CXCL9. IL-17 levels were similar in both ODS and controls. Therefore, ODS demonstrated heightened innate and Th1 immune activity. CONCLUSION: ODS demonstrated both innate immune and Th1 inflammatory endotypes. Further studies are needed to explore ODS immunopathobiology and its potential impact on ODS management.

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair.

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.

Radiographic protrusion of dental implants in the maxillary sinus and nasal fossae: A multidisciplinary consensus utilising the modified Delphi method.

The aim of the present study was to generate an international and multidisciplinary consensus on the clinical management of implant protrusion into the maxillary sinuses and nasal fossae. A total of 31 experts participated, 23 of whom were experts in implantology (periodontologists, maxillofacial surgeons and implantologists), 6 were otolaryngologists and 2 were radiologists. All the participants were informed of the current scientific knowledge on the topic based on a systematic search of the literature. A list of statements was created and divided into three surveys: one for all participants, one for implant providers and radiologists and one for otolaryngologists and radiologists. A consensus was reached on 15 out of 17 statements. According to the participants, osseointegrated implants protruding radiographically into the maxillary sinus or nasal fossae require as much monitoring and maintenance as implants fully covered by bone. In the event of symptoms of sinusitis, collaboration between implant providers and otolaryngologists is required. Implant removal should be considered only after pharmacological and surgical management of sinusitis have failed.

Odontogenic Sinusitis is a Common Cause of Operative Extra-Sinus Infectious Complications.

BACKGROUND: Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized. OBJECTIVE: To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases. METHODS: A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed. RESULTS: Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization. CONCLUSION: ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected.